Susan G Komen  
I've Been Diagnosed With Breast Cancer Someone I Know Was Diagnosed Share Your Story Join Us And Stay Informed Donate To End Breast Cancer
    Home > Research & Grants > Grants Program > Research Grants > Research Grants Awarded > Abstract

    Research Grants Awarded

    Boosting Immunity to Metastatic Breast Cancer Using Targeted T Cells: A Phase II Clinical Trial

    Study Section:
    Treatment

    Scientific Abstract:
    In a phase I clinical trial, we have treated women with metastatic breast cancer with their own ex vivo expanded, anti-CD3 activated T cells (ATC) that had been armed with a bispecific antibody, anti-CD3 x Herceptin® (Her2Bi), in order to mediate specific killing of their tumor cells. In addition to observed decreases in clinical tumor markers such as CA 27.29 and Carcinoembryonic antigen (CEA), immune evaluations during and after treatment indicate that many of these women developed enhanced immunity directed specifically against breast cancer cells. Extensive disease burden, however, presents limitations to solely using an immunotherapeutic approach for successfully treating metastatic breast cancer. This is not surprising given that even those women with Her2/neu positive disease who receive Herceptin® in addition to their chemotherapeutic regimens will eventually progress (median time to progression: 3-3.5 months). More aggressive treatment strategies, therefore, are needed for women with refractory metastatic breast cancers. Peripheral blood stem cell transplant (PBSCT) permits the use of high-dose chemotherapy (HDC) that could not otherwise be given without bone marrow rescue. Accordingly, HDC combined with PBSCT has resulted in more responses in chemo-refractory disease than typically achieved with standard chemotherapy. Our plan, therefore, is to first boost patient immunity (i.e. ?vaccinate?) against breast cancer cells by treating with Her2Bi-armed ATC, collect a portion of these pre-immunized cells after completion of treatment so that they can be further expanded in culture, treat the patient with HDC followed by PBSCT to reduce the tumor burden, and then transfer the pre-immunized ATC back to the patient. We hypothesize that this transfer of pre-immunized cells after PBSCT will accelerate immune reconstitution and enhance immune-mediated killing of residual tumor cells that may have escaped treatment with HDC, thereby prolonging progression-free survival in these women for whom there are limited therapeutic options.

    Lay Abstract:
    In an ongoing clinical trial, we have treated women with metastatic breast cancer with their own activated T cells (ATC)-immune cells that attack cancer cells-that have been coated with a bispecific antibody, Her2Bi, an agent that allows the T cells to target and kill breast cancer cells. In addition to observing decreases in clinical tumor markers such as CA 27.29 and Carcinoembryonic antigen (CEA), immune evaluations during and after treatment indicate that many of these women developed enhanced immunity directed specifically against breast cancer cells. Extensive disease burden, however, presents limitations to solely using an immunotherapeutic approach for successfully treating metastatic breast cancer. This is not surprising given that even those women with Her2/neu positive disease who receive Herceptin® in addition to their chemotherapeutic regimens will eventually progress (median time to progression: 3-3.5 months). More aggressive treatment strategies, therefore, are needed for women with metastatic breast cancers that do not respond to standard therapies. Peripheral blood stem cell transplant (PBSCT) is a procedure whereby the patient?s own stem cells (SC) are collected, stored and then transplanted after they receive chemotherapy. PBSCT permits the use of high dose chemotherapy (HDC), which is more potent for killing tumor cells than standard chemotherapy doses. Accordingly, HDC combined with PBSCT has resulted in more effective clinical responses than seen with standard chemotherapy. Our plan, therefore, is to first boost patient immunity (i.e. ?vaccinate?) against breast cancer cells by treating with Her2Bi-armed ATC, collect a portion of these pre-immunized cells after treatment so that they can be further expanded in culture, treat the patient with HDC followed by PBSCT to reduce the tumor burden, and then transfer the pre-immunized ATC back to the patient. We believe that this transfer of pre-immunized cells after PBSCT will accelerate the recovery of the patient's immune system after HDC as well as enhance immune-mediated killing of residual tumor cells that may have escaped treatment with HDC, thereby prolonging progression-free survival in these women for whom there are limited therapeutic options.